Clinical role of N otch signaling pathway in intraductal papillary mucinous neoplasm of the pancreas

Background and Aim This study was performed to elucidate the expression of the Notch signaling pathway and its correlations to clinicopathological factors of intraductal papillary mucinous neoplasms ( IPMN s). It is incontrovertible that regulatory T cells ( T regs) play an important role in tumor immunity. However, the whole mechanism of control of peripheral T regs remains unclear. It is also known that the N otch signaling pathway is involved in T reg suppressor function. Moreover, IPMN s have a high malignant potential. Methods Peripheral blood samples and resected specimens from 18 patients with IPMN were evaluated. All patients were pathologically diagnosed with IPMN . Resected specimens were immunohistochemically evaluated (anti‐ N otch1, anti‐ N otch2, and anti‐ N otch2‐intracellular domain antibody staining) and compared in terms of clinicopathological factors. Peripheral T reg populations were analyzed with an automated flow cytometer. Results Disease‐free survival was significantly worse in the N otch1 high‐expression group ( P  = 0.023). N otch2 family expressions were higher in intraductal papillary mucinous carcinoma ( IPMC ) than in intraductal papillary mucinous adenoma ( IPMA ) ( N otch2, P  = 0.012; N otch2‐intracellular domain, P  = 0.036). J agged1 expression was significantly higher in IPMC than in IPMA ( P  < 0.05) and was significantly related to recurrence. The T reg population in peripheral blood was higher in patients with IPMC than in those with IPMA ( P  < 0.01). Conclusions N otch signaling, especially J agged1 expression, reflects IPMN aggressiveness. Our data may suggest that the N otch signaling pathway is a key pathway that determines IPMN pathological aggressiveness and reflects the peripheral T reg population.